Solution phase studies towards the synthesis of triarylamine oligomers using a germanium linker on a solid support

Article abstract of DOI:10.1016/j.tetlet.2005.07.150

In this letter, we describe the iterative solution phase synthesis of a triarylamine trimer as proof of concept towards the synthesis of oligomeric materials by solid-phase synthesis. Our model system utilises the stability of germanium linkers to nucleophilic conditions to develop efficient steps towards oligomer synthesis via (i) selective deprotection of tert-butyl-dimethyl-silyl ether (OTBDMS) functionality, (ii) conversion to reactive trifluoromethanesulfonate (triflate) functionality and (iii) Suzuki cross-coupling reactions.

Full text of DOI:10.1016/j.tetlet.2005.07.150

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6717–6721
Solution phase studies towards the synthesis of
triarylamine oligomers using a germanium linker on a solid support
a,
a
a
b
*
´
R. Anemian, D. C. Cupertino, P. R. Mackie and S. G. Yeates
aMerck Chemicals Ltd, LC-Manchester Technical Centre, Hexagon Tower, Blackley, Manchester M9 8ZS, UK
bSchool of Chemistry, The University of Manchester, Manchester M13 9PL, UK
Received 28 April 2005; revised 26 July 2005; accepted 26 July 2005
Available online 16 August 2005
Abstract—In this letter, we describe the iterative solution phase synthesis of a triarylamine trimer as proof of concept towards the
synthesis of oligomeric materials by solid-phase synthesis. Our model system utilises the stability of germanium linkers to nucleo-
philic conditions to develop efficient steps towards oligomer synthesis via (i) selective deprotection of tert-butyl-dimethyl-silyl ether
(OTBDMS) functionality, (ii) conversion to reactive trifluoromethanesulfonate (triflate) functionality and (iii) Suzuki cross-coupling
reactions.
Ó 2005 Published by Elsevier Ltd.
1. Introduction
quite inefficient, resulting in very low yields. Recent
publications10–12 have clearly demonstrated both the
advantages and the versatility of solid-phase organic
synthesis (SPOS) in the iterative preparation of p-conju-
gated oligomers. The major benefits over traditional
solution phase techniques include (i) ease of purification
of the target oligomer, (ii) ability to use excess reagents
(which can be easily removed by filtration) to drive reac-
tions to completion, (iii) prevention of homocoupling
reactions by virtue of site isolation of growing oligomer
chains and (iv) the amenability of the process to auto-
mation. However, a potential drawback of the SPOS
technique is that cleavage of the product from the resin
can leave a functional group on the oligomer, which can
have a dramatic outcome on its properties. To circum-
vent this problem, some workers have developed trace-
less linker systems, which provide an elegant means to
cleave oligomers from solid supports, whilst leaving no
undesirable functionality on the target material.13
Conjugated oligomers are at the core of several emerg-
ing technologies as active materials for electronic and
photonic applications such as organic light-emitting
diodes,1 organic field-effect transistors2 and photovol-
taic devices.3 Key properties in such materials include
stability and processability during fabrication, high
charge mobility in a device and perhaps most critically,
high purity.4 A number of oligomeric materials have
been reported in the literature, including alkylthio-
phenes,5 fused thiophenes,6 dialkylfluorenes7 and tri-
arylamines.8 Of these materials, triarylamine oligomers
have been shown to offer an excellent compromise
between performance and stability.9 Solution phase
chemistry has been used successfully to synthesise a
variety of oligomers using repetitive transition metal
catalysed cross-coupling, however, control over the
structure of such materials can be exceedingly difficult.
The result of this lack of control is that some materials
have been difficult to synthesise using traditional
techniques, or require arduous purification to achieve
the required purity for electronics applications. Indeed,
the purification process based on column chromatogra-
phy of intermediates is time consuming and sometimes
In this communication, we describe solution phase stud-
ies directed towards the development of the solid-phase
synthesis of high purity triarylamine oligomers using a
germanium linker on a solid support. This new class
of linker, which can be readily cleaved by protodegermyl-
ation of the Ge–Ar bond, fulfils the criteria required of a
traceless linker.14 In addition, germanium linkers dis-
play an enhanced stability towards both bases and
nucleophiles and a greater susceptibility to electrophilic
ipso-demetallation than their silicon counterparts.15
Keywords: Triarylamine; Oligomers; Germanium; Solid phase.
Corresponding author. Tel.: +44 (0)161 721 1028; fax: +44 (0)161
720 9138; e-mail: remi.anemian@merckchem.com
*
0040-4039/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.07.150

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R. Ane´mian et al. / Tetrahedron Letters 46 (2005) 6717–6721
These properties arise due to the greater b-effect of ger-
manium16 when compared with silicon based systems.
By way of a contrast, arylsilane based linkers require
harsh conditions to effect cleavage of electron-deficient
aromatic systems.17 Recent developments on the synthe-
sis of germanium-based linkers have allowed the Ôfine-
tuningÕ of such linkers for specific applications thus
allowing them to show a wider potential in solid-phase
synthesis.18
of the chosen monomer at stage (ii). Our approach uses
conditions which are compatible with the germyl linker,
in that electrophilic reagents are avoided due to the sen-
sitivity of the linker to ipso-degermylation. Typically,
transition metal mediated couplings require the presence
of a halogen substituent on one or both of the coupling
partners. Such halogen substituents are usually intro-
duced by way of an electrophilic halogenation of the
monomer, which would result in cleavage of the germa-
nium linker.14 Suzuki cross-coupling reactions using
pseudohalogens such as a triflate group represent a use-
ful alternative as they may be introduced into the grow-
ing oligomer by a means that is compatible both with
the requirements of the germanium linker, and with
the protection strategy employed in this synthetic
scheme. Specifically, aryl-triflate reagents are accessible
from phenols and can be readily incorporated into both
the linker and monomer units. Prior to coupling, the
phenol functionality is protected as an OTBDMS group
in order to avoid any interference which may occur with
the Suzuki cross-coupling conditions. The choice of the
protecting group was based on the fact that protection
and deprotection should not affect the germyl linkage
to the solid support. It has been noted in the literature
that there is an orthogonal susceptibility of a-silyl and
a-germyl substituted thiophene derivatives towards
nucleophilic ipso-protodemetallation.19 In this work,
we demonstrate the selectivity between a-silyloxy and
a-germyl substituted triarylamines towards cleavage by
nucleophiles.
2. Results and discussion
The synthetic approach we used in the iterative solution
phase synthesis of a model triarylamine oligomer is out-
lined in Scheme 1 and may be summarised by the follow-
ing steps: (i) synthesis and activation of the germanium
linker system, (ii) coupling of the first protected mono-
mer to the linker, (iii) deprotection of the tert-butyl-
dimethyl-silyl ether (OTBDMS) group, (iv) conversion
to an activated trifluoromethanesulfonate (triflate) cou-
pling precursor followed by a repeat of (ii) with cross-
coupling of a second, third, nth protected (or (v) an
end-capping) monomer and lastly (vi) cleavage of the
oligomer from the germanium-based linker. In this
scheme, steps (ii), (iii) and (iv) may be repeated as often
as required to build-up the target oligomer.
Assembly of the oligomer is a step-wise process in which
each monomer unit is added sequentially through a
transition metal mediated coupling. Such an approach
is directly transferable to the solid phase, where high
purity oligomers with well-defined structures (i.e., no
deletions) may be produced by simply using an excess
The synthesis and activation of the germanium linker
system is described in Scheme 2. The synthesis of the lin-
ker began from {2-[4-(2-ethoxy-ethoxy)-phenyl]-ethyl}-
Ge
Cl
1
O
R =
R
OEt
(i)
Iterate x n
Ge
R
Ge
Ge
R
CH3
R
Y = CH3
(v)
7
Y = OTBDMS
(ii)
6
X
3
n
(ii)
N
OTf
N
5
11
O
B
N
Y
O
(vi)
n=1
n=2
X = OTBDMS
13
14
15
16
(iii)
(iv)
X = OH
X = OTf
17
18
CH3
3
N
12
Scheme 1. Key steps in the iterative solution phase synthesis of triarylamine oligomer 12 as a model system for the solid phase. (i) See Scheme 2 for
synthesis and activation of linker system, (ii) Pd(Ph3)4, Na2CO3(aq) (2 M), 1,2-dimethoxyethane, 80 °C, (iii) NBu4F, THF, ambient temperature (iv)
trifluoromethane sulfonic anhydride, pyridine, 0 °C, (v) Pd(Ph3)4, Na2CO3(aq) (2 M), 1,2-dimethoxyethane, 80 °C, (vi) trifluoroacetic acid (1% in
dichloromethane).

R. Ane´mian et al. / Tetrahedron Letters 46 (2005) 6717–6721
6719
Br
OTBDMS
2
(i)
Li
OTBDMS
Ge
Ge
Cl
(ii)
EtO
EtO
OTBDMS
O
O
3
1
(iii)
Ge
(iv)
Ge
EtO
EtO
OTf
OH
O
O
5
4
Scheme 2. Synthesis and activation of the model linker system: (i) n-BuLi (2.5 M in hexanes), THF, À78 °C, (ii) toluene, ambient temperature, (iii)
NBu4F, THF, ambient temperature, (iv) trifluoromethane sulfonic anhydride, pyridine, 0 °C.
dimethyl-germyl-chloride,18 1. This was chosen for the
solution phase model because it is possible to develop
a synthetic methodology using this linker, which may
be transferred directly to the solid phase. In the model
linker (Scheme 2), the ethoxyether substituent provides
a solution phase surrogate, which mimics polyethylene
glycol (PEG) based resins such as QuadragelTM20 or Hyp-
ogelTM. By transmetallation of {2-[4-(2-ethoxy-ethoxy)-
phenyl]-ethyl}-dimethyl-germyl-chloride 1 with lithiated
(4-bromo-phenoxy)-tert-butyl-dimethyl-silane21 2, it is
possible to synthesise the OTBDMS functionalised lin-
ker 3 in 77% yield. It was then possible to establish
the optimum conditions to (i) deprotect the OTBDMS
group and (ii) convert the resultant phenol into the cor-
responding triflate without affecting the a-germyl link-
age. The selectivity of cleavage of the OTBDMS group
over the a-germyl linker was achieved using tetrabutyl-
ammonium fluoride (TBAF), confirming the relative
stability of aryl-germanes towards nucleophiles when
compared to aryl-siloxanes. Deprotection of the
OTBDMS group was achieved in 76% yield to give the
corresponding phenol 4 with no detectable cleavage of
the germyl linker. Finally, conversion of the phenol 4
into the triflate derivative 5 was achieved using trifluo-
romethanesulfonic anhydride in anhydrous pyridine.
dimethylaniline, 1-iodo-4-bromobenzene and 4-bromo-
phenoxy-tert-butyldimethylsilane21 2. The resultant
intermediate 9 was then converted to the corresponding
boronic acid ester 6 using standard conditions. The sec-
ond monomer, [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaboro-
lan-2-yl)-phenyl]-di-p-tolylamine, 7, was prepared
(Scheme 3(b)) in two steps from di-p-tolylamine and 1-
iodo-4-bromobenzene by a standard Ullmann proce-
dure.23 Again, the (4-bromo-phenyl)-di-p-tolyl-amine
intermediate, 10, was converted to the corresponding
boronic acid ester 7 in good yield.
Aryl-triflate functionalised compounds are known to
undergo very clean and efficient Suzuki cross-coupling
reactions catalysed by palladium.24 However, literature
procedures for this cross-coupling reaction were found
to be incompatible with the germanium linker. This
was attributed to the presence of halogenated alkali me-
tal salts in such procedures. We subsequently developed
a procedure which omitted the use of such salts and
allowed us to couple the first protected triarylamine
monomer 6 to the activated linker 5 in 84% yield. No
detectable cleavage of the germyl linker was observed
under these conditions. A minor impurity was observed,
namely,
4-({2-[4-(2-ethoxy-ethoxy)-phenyl]-ethyl}-di-
methyl-germanyl)-phenol, 4, which was formed by the
competitive hydrolysis of the triflate functionality in 5.
To drive the cross-coupling reaction to completion, it
would be possible to re-activate the phenol to the corre-
sponding triflate derivative 5 (Scheme 2) and react this
further with a monomer. Such a procedure would be
particularly useful when carrying out this reaction on
a polymer support and is directly analogous to double
coupling strategies described in the literature.25
To apply our step-wise growth strategy based on Suzuki
cross-coupling, we developed two triarylamine mono-
mers, the first, 6, was functionalised with (i) a boronic
acid ester and (ii) a protected phenol group, which was
subsequently deprotected and activated as a triflate pre-
cursor for the next coupling. The second monomer, 7,
features only the boronic acid ester reactive group.
Monomer 6 was designed to grow the oligomer in a
controlled step-wise manner whereas monomer 7 was
designed to Ôend-capÕ the oligomer after the growth
process. Monomer 6 was prepared (Scheme 3a) in three
steps using Buchwald22 reaction conditions from 2,4-
As proof of concept of the step-wise construction of an
oligomer, we determined to synthesise a triarylamine tri-
mer 11 (Scheme 1). Typical yields for each iterative step:

6720
R. Ane´mian et al. / Tetrahedron Letters 46 (2005) 6717–6721
Br
OH
(i)
Br
OTBDMS
2
(ii)
N
H
OTBDMS
(a)
8
NH2
(ii)
Br
I
O
(iii)
B
N
OTBDMS
Br
N
OTBDMS
O
9
6
Br
I
(b)
N
H
Br
N
(iv)
10
(iii)
O
B
N
O
7
Scheme 3. Synthesis of triarylamine monomers: (a) [4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-
phenyl]-p-tolyl-amine 16 and (b) [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-di-p-tolyl-amine 18; (i) tert-butyldimethylsilylchloride,
imidazole, DMF, ambient temperature, (ii) NaOBut, Pd2dba3, rac-binap, toluene, 100 °C, (iii) n-BuLi (2.5 M in hexanes), THF, À78 °C,
2-isopropoxy-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane, (iv) KOH, o-xylene, CuCl, 1,10-phenanthroline, 100 °C.
Table 1. Typical yields (%) of iterative steps for step-wise growth of triarylamine oligomer 11
Number iterative steps
0
1
2
(i) Yield of cleavage of TBDMS protecting group (%)
(ii) Yield of conversion to triflate precursor (%)
(iii) Yield of cross-coupling reaction (%)
76
87
84
90
86
71
75
92
75
(i) cleavage of the OTBDMS group, (ii) conversion of
the resultant phenol to a triflate precursor and (iii)
cross-coupling with another monomer are summarised
in Table 1.
3. Conclusion
In summary, we have described the step-wise prepara-
tion of triarylamine oligomers in solution as proof of
concept towards the synthesis of such oligomers on a
solid support. Our model system utilises a germanium
linker, which demonstrates a greater stability to nucleo-
philic conditions relative to arylsiloxane functionality.
We have established the efficiency and the compatibility
of the key steps in the oligomer build-up with the germa-
nium linker, namely (i) selective deprotection of the
The final step of the synthesis is the release of the oligo-
mer from the germanium-based linker by electrophilic
ipso-degermylation. By treatment with trifluoroacetic
acid (TFA), quantitative cleavage of the aryl-germa-
nium bond is achieved, yielding the H-capped triaryl-
amine trimer 12.

R. Ane´mian et al. / Tetrahedron Letters 46 (2005) 6717–6721
6721
8. Allen, J. V.; Fergus, J.; Leeming, S. W.; Morgan, J. D.;
Thomas, M. WO99/35537, Avecia Ltd, 01.07.1999.
9. Leeming, S. W.; Veres, J.; Morgan, J. D.; Wright, E.;
Brown, B. A. WO01/68740, Avecia Ltd, 20.09.2001.
OTBDMS group, (ii) conversion of the resultant phenol
to a triflate coupling precursor and (iii) cross-coupling.
We are currently transferring this model to a solid sup-
port and adapting the synthetic strategy to accommo-
date other monomers.
´
10. Malenfant, P. R. L.; Frechet, J. M. Chem. Commun. 1998,
2657–2658.
11. Huang, S.; Tour, J. M. J. Org. Chem. 1999, 64, 8898–
8906.
12. Kirschbaum, T.; Briehn, C. A.; Ba¨uerle, P. J. Chem. Soc.,
Perkin Trans. 1 2000, 1211–1216.
Acknowledgements
The authors gratefully acknowledge the support and
advice provided by Dr. Alan Spivey and Dr. David
Turner. R.A. acknowledges the European Commission
for a Marie Curie Fellowship (G5TR-CT-2000-00036).
13. Plunkett, M. J.; Ellman, J. A. J. Org. Chem. 1995, 60,
6006–6007.
14. Spivey, A. C.; Diaper, C. M.; Rudge, A. J. Chem.
Commun. 1999, 835–836.
15. Spivey, A. C.; Diaper, C. M.; Adams, H.; Rudge, A. J.
J. Org. Chem. 2000, 65, 5253–5263.
16. Lambert, J. B.; Zhao, Y.; Emblidge, R. W.; Salvador, L.
A.; Liu, X.; So, J.-H.; Chelius, E. C. Acc. Chem. Res. 1999,
32, 183–190.
17. Plunkett, M. J.; Ellman, J. A. J. Org. Chem. 1997, 60,
2885–2893.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2005.07.150.
18. Spivey, A. C.; Turner, D. J.; Turner, M. L.; Yeates, S.
Synlett 2004, 1, 111–115.
19. Spivey, A. C.; Turner, D. J.; Turner, M. L.; Yeates, S.
Org. Lett. 2002, 4, 1899–1902.
20. QuadragelTM (Avecia/Reaxa Ltd, www.reaxa.com) is a PS-
crosslinked based resin with hydroxyl-terminated PEG
grafts containing four oxyethyl units.
References and notes
1. Kraft, A.; Grimsdale, A. C.; Holmes, A. B. Angew. Chem.,
Int. Ed. 1998, 37, 402–428.
21. Pettit, G. R.; Grealish, M. P.; Jung, M. K.; Hamel, E.;
Robin, R. K.; Chapuis, J.-C.; Schmidt, J. M. J. Med.
Chem. 2002, 45, 2534–2542.
22. Harris, M. D.; Buchwald, S. L. J. Org. Chem. 2000, 65,
5327–5333.
23. Goodbrand, H. B.; Hu, N.-X. J. Org. Chem. 1999, 64,
670–674.
24. Oh-e, T.; Miyaura, N.; Suzuki, H. J. Org. Chem. 1993, 58,
2201–2208.
2. Dimitrakoupolos, C. D.; Mascaro, D. J. IBM J. Res. Dev.
2001, 45, 11–27.
3. Winder, C.; Sariciftci, N. S. J. Mater. Chem. 2004, 14,
1077–1086.
4. Briehn, C. A.; Kirschbaum, T.; Ba¨uerle, P. J. Org. Chem.
2000, 65, 352–359.
5. McCullough, R. D. Adv. Mater. 1998, 10, 1–24.
6. Laquindanum, J. G.; Katz, H. E.; Lovinger, A. J. J. Am.
Chem. Soc. 1998, 120, 664–672.
´
25. Dettin, M.; Pegoraro, S.; Rovero, P.; Bicciato, S.;
Bagno, A.; Di Bello, C. J. Pept. Res. 1997, 49, 103–
111.
7. Donat-Bouillud, A.; Levesque, I.; Tao, Y.; DÕIorio, M.;
´
Beaupre, S.; Blondin, P.; Ranger, M.; Bouchard, J.;
Leclerc, M. Chem. Mater. 2000, 12, 1931–1936.